Structure and hydrogen bond network analysis of Cyclooxygenase-Pyrazines Complex by molecular dynamics method

Abstract

We reported that simple alkyl- and arylpyrazines were showed the 50% inhibitory concentration towards arachidonic acid-induced and collagen-induced aggregation of rabbit blood platelet in vitro. Among the 48 pyrazine derivatives, 2,3-bis(p-methoxyphenyl)pyrazines showed the most potent inhibitory activity. Molecular dynamics (MD) simulations of the complexes of 2OYU with compound 42 and 1HT5 with flurbiprofen methyl ester were performed. From the MD simulation results, the binding modes, structural changes, and intermolecular hydrogen bonds have revealed the molecular interactions explaining the differences in the cavity size of the active site by ligands used. In order to clearly the interaction of the COX-Ligands, the InterFragment Interaction Energy (IFIE) analysis was calculated by Fragment Molecular Orbital method. Consequently, relatively strong interaction energies of the ARG120-ligand calculated to be -19.4 kcal/mol, SER353-ligand calculated to be -12.9 kcal/mol and ILE523-ligand calculated to be -11.9 kcal/mol.